What Does Overmethylation Feel Like?

Hi Lotus, I was thanking you for the instructions on how to do quotes. I'm techno-slow, but still trainable.

Yes, I see people are combining folates. I'll consider trying low dose folinic acid alone in the future out of curiosity, but I'm going to wait...I need to reduce this elevated serum folate. ( cancer in the family)

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Oh, ok. I forgot I said that. I didn't realize too much folate could cause problems for cancer. I usually thought of methylation as good due to possible lowering of homocysteine. I know one person who is COMT ++ and is taking a high amount of methylcobalamin due to B12 deficiency symptoms and she was having problems with even a small amount of folinic acid. Everyone's different, but it's possible you could have the same issues. The reason Rich recommends folinic acid is for nucleotides which are used for creating RNA and DNA and also making ATP. At higher doses, dbkita said folinic acid is for CNS penetration and saturation just as the high doses of methylfolate is used for by some people here. I asked him if that was the same thing as neurological healing and he said yes. I think I have more questions about that, but I'll ask you later in a private conversation because I don't wan to tie up this thread anymore and also because I've asked you a lot of questions already.

While it does seem that some people do need relatively high doses, other people either don't need as high a dose and/or are unable to tolerate a higher dose due to health issues. Since I suspect many people who come across this thread are having trouble with dosage, I thought I'd share an inspiring story I came across recently. I'm not necessarily recommending that people take doses as low as this or suggesting that others will have the same success as this person. Most people at the very least are able to tolerate the starting doses Rich recommends (around 90% according to a study done with an older version of Rich's protocol).

Several years ago I told Rich that, if it were possible to start the methylation supplements with just ONE molecule, I would do it! Well, I didn't start then.

But in late January, I decided to start FolaPro and methylcobalamin at miniscule doses.

I should say that I have a very long history with extreme multiple chemical sensitivities and food intolerances (could only eat a handful of foods, and I was basically a prisoner in my home to avoid chemical exposures for a few years) so I have lots of experience getting HUGE reactions from tiny specks of medications and supplements scraped off of a tablet, or emptied from a capsule.

The weakness and fatigue component of this illness started about 20 years ago. The most significant improvement I got was when I was treated with chemotherapy (Rich has pointed out that folinic acid is infused along with the meds). I have also been helped by doxycycline.

So, in late January of this year, I opened a 1,000 mcg capsule of methylcobalamin, removed a speck, and broke off a very small fraction of a Folapro tablet. I emptied both of these into one cup of water. Then, I measured a quarter teaspoon and put it under my tongue. I could only hold it for a few seconds and I have had to stop this sublingual method because my bottom teeth would ache and ache.

To give some perspective on just how small a dose this is, I have only used 4 FolaPro tablets since I began 3 months ago.and realize, that all but approximately 1/200th of that ended up down the drain!

I know that this sounds odd and perhaps unbelievable. But I have a difference in energy. Im not sure where my boundaries are for weakness/fatigue. This in itself is very unusual since most days in the past 20 years I have been right at or even beyond that boundary.

Its very exciting for me but I am resisting the impulse to increase the dose. The idea that some kind of switch has been flipped really resonates for me. I am cautiously increasing my exercise, without forcing it. Usually, when I have walked my dogs, I have been grateful for their constant stopping and sniffing. Now, I find that I am impatient with them, and try to walk without them so I can go faster(!!!). I have even experienced muscle soreness from walking faster and yet I have NOT experienced PEM. Wow.

Rich, I want to thank you for all the information you have provided. I have been following your ideas for years now; I just wish I had acted sooner. The reason I am writing this is to encourage those who may be afraid to gamble with their current state of health. I have enjoyed a half life for several years and I didnt want to risk it on something that could potentially make me feel worse, even for a while. I believe that starting at a VERY small dose is a rational strategy for others like me.

I don't know if you've tried some extra B3 and B2, but it may help with the overmethylation problems.

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I'm taking a lot of B3. I'm not sure if helps or not, but I'm taking a low methylation dose so I'm not sure if I'm really in danger of overmethylation. My other symptoms (possibly adrenal related or Lyme CNS) are very similar to overmethylation symptoms. B2 (and especially R5P) will increase methylation though. Maybe B2 helps you for other reasons. This is from dbkita

Last year switching from 100 mg b2 to 100 mg r5p sodium was one of the main changes that forced me into hypokalemia and not even 11 grams [of potassium] per day could contain it. More recently I went to two split two doses of 50 mg of riboflavin and while I had more verve and energy at first, within a few days I had charlie horses and terrible foot cramps.

Be warned that b2 absorption is not linear after 30 mg. It saturates pretty quickly. 100 mg at once might net you 40-50 mg total. That is why I thought to split doses and bam. R5p sodium has no such saturation and high oral bioavailability which is probably why it was so devastating to switch to 100 mg of that almost a year ago.

Lotus97;
Hi Lotus, yes, I think the B2 helps on several levels; metabolizing folate, amines, and for me, it did seem to become depleted when taking large amounts of B12/folate. I didn't notice that it lowered potassium, but I'm taking plenty now.

I see in Freddd's recent thread that he developed what looks to be increased inflammation from taking extra B2 and B3. It floors me that the same substances can be anti-inflammatory to some, and pro-inflammatory to others. But it's true, no doubt.

Say, I wonder what adrenal type symptoms you are having ? Cortisol is a most powerful anti-inflammatory hormone. But, I know of some Addisonians who still suffer allergies, asthma, etc. But, maybe you are referring to increased NE? From what I understand about it,( and what I've experienced), cortisol modulates epinephrine. Meanwhile though, it's actions are so vast, it would be better to find a more specific modulator, I think.

Say, I wonder what adrenal type symptoms you are having ? Cortisol is a most powerful anti-inflammatory hormone. But, I know of some Addisonians who still suffer allergies, asthma, etc. But, maybe you are referring to increased NE? From what I understand about it,( and what I've experienced), cortisol modulates epinephrine. Meanwhile though, it's actions are so vast, it would be better to find a more specific modulator, I think.

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Based on what dbkita told me, it seems like it's from NE/norepinephrine. The best way I can describe it is the fight or flight response. Low cortisol is one of the causes of high NE, but there are other causes as well. Norepinephrine can also lower GABA which would increase anxiety. I'm not sure if that's what's going on with me as far as the lowered GABA and anxiety. Interestingly, for some people, increasing norepinephrine will help them with anxiety. There are a lot of causes of anxiety, but it seems to go along with my adrenal symptoms. Lyme could also be involved.http://www.mentalhealthandillness.com/tnaold.html

Late stage neuropsychiatric Lyme disease can best be conceptualized as a disseminated and progressive, (predominately sub-cortical), encephalopathy. Animal studies and autopsies have contributed to our understanding of the disease process. (25,26,27,28). As symptoms progress, additional symptoms occur and increase in severity. These symptoms may be categorized in the following manner:1. Brain Stem

A variety of stressful events, including emotional stress, cause a marked increase in noradrenaline release in several brain regions, and especially in the hypothalamus, amygdala and locus coeruleus, in the rat brain. These findings suggest that an increased noradrenaline release could be closely related to the provocation of negative emotions such as anxiety and/or fear.

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When I had the bad experience with methylfolate last fall my symptoms were very similar, but I know it's different now because back then I wasn't experiencing those symptoms at all until I started the methylfolate. After I stopped the methylfolate I experienced mostly fatigue. Then after my second methylation attempt the anxious, wired symptoms started up again and continued even after I stopped methylation. The symptoms during the second time weren't as bad as the first time since I wasn't taking any methylfolate.

Hi Lotus, yes, I think the B2 helps on several levels; metabolizing folate, amines, and for me, it did seem to become depleted when taking large amounts of B12/folate. I didn't notice that it lowered potassium, but I'm taking plenty now.

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Were you taking B2 in the form of riboflavin or R5P?

I see in Freddd's recent thread that he developed what looks to be increased inflammation from taking extra B2 and B3. It floors me that the same substances can be anti-inflammatory to some, and pro-inflammatory to others. But it's true, no doubt.

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I don't think it was the B2 that caused the inflammation directly, but rather indirectly through methylation. I assume you knew that, but I understand what you're saying. Same thing with methylcobalamin. Methylcobalamin can protect against excitotoxicity, but combined with too much methylfolate and/or methyl donors methylcobalamin will cause excitotoxicity.

I wonder if part of Freddd's reaction to the B2 (and maybe B3) was due to deficiency. He seems to be proposing that taking nutrients that you're deficient in will cause "start up" symptoms and possibly increase methylation. I don't think there's any doubt that taking nutrients you're deficient in can sometimes cause "start up", but if that's involved in methylation I'd be curious to know. One of the theories about hypersensitivity to methylfolate (besides COMT) is that it's due to deficiency. For me the symptoms went on for at least 5 weeks until stopped. I was taking 1500 mcg of folic acid at the same time so maybe it somehow prolonged the deficiency.

quote="Lotus97, post: 351275, member: 8815"]Based on what dbkita told me, it seems like it's from NE/norepinephrine. The best way I can describe it is the fight or flight response. Low cortisol is one of the causes of high NE, but there are other causes as well. Norepinephrine can also lower GABA which would increase anxiety. I'm not sure if that's what's going on with me as far as the lowered GABA and anxiety. Interestingly, for some people, increasing norepinephrine will help them with anxiety. There are a lot of causes of anxiety, but it seems to go along with my adrenal symptoms. Lyme could also be involved.http://www.mentalhealthandillness.com/tnaold.html

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I can see why you are having such a challenge with discerning the origin of the symptoms. It looks like Lymes Disease is all encompassing. I have no experience with it, but my BIL contracted it, and among other things, one side of his face became paralyzed and sagged. ( this is all he told me). I think the standard antibiotic treatment worked for him, but I believe he was treated early.

When I had the bad experience with methylfolate last fall my symptoms were very similar, but I know it's different now because back then I wasn't experiencing those symptoms at all until I started the methylfolate. After I stopped the methylfolate I experienced mostly fatigue. Then after my second methylation attempt the anxious, wired symptoms started up again and continued even after I stopped methylation. The symptoms during the second time weren't as bad as the first time since I wasn't taking any methylfolate

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I think I'm having a similar situation. There are cases of unmetabolized folate causing problems, but it's thought to be folic acid. There's some doubt though. Since I've had trouble with methylfolate too, I'm going to suspend my use of it for some months. ( Hopefully, when we get our 23and me results, we'll get a clue.)

Were you taking B2 in the form of riboflavin or R5P?

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I've mostly taken B2, riboflavin, but I have some R5P that I've tried a little. ( don't know yet)

I don't think it was the B2 that caused the inflammation directly, but rather indirectly through methylation. I assume you knew that, but I understand what you're saying. Same thing with methylcobalamin. Methylcobalamin can protect against excitotoxicity, but combined with too much methylfolate and/or methyl donors methylcobalamin will cause excitotoxicity

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Yes, thanks for clarifying, from reading about B2, and reading dbkita's posts, it looks to be an indirect action. ( Yeesh, this is some technical stuff for me... I'm used to being a "left fielder".)

I wonder if part of Freddd's reaction to the B2 (and maybe B3) was due to deficiency. He seems to be proposing that taking nutrients that you're deficient in will cause "start up" symptoms and possibly increase methylation. I don't think there's any doubt that taking nutrients you're deficient in can sometimes cause "start up", but if that's involved in methylation I'd be curious to know. One of the theories about hypersensitivity to methylfolate (besides COMT) is that it's due to deficiency. For me the symptoms went on for at least 5 weeks until stopped. I was taking 1500 mcg of folic acid at the same time so maybe it somehow prolonged the deficiency.

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I don't know, but he surely had a strong negative reaction, but, if anyone can figure it out, I guess he and dbkita can!

I can see why you are having such a challenge with discerning the origin of the symptoms. It looks like Lymes Disease is all encompassing.

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Yeah, it's very tricky unraveling everything. Lyme can directly cause symptoms, but then it can also indirectly cause symptoms such as causing adrenal or thyroid issues which then cause symptoms. It seems likely that Lyme has caused my chronic insomnia which caused symptoms. I attribute a huge part of my recovery to getting enough sleep consistently for over a year. And part of my relapse I attribute to lack of sleep due to changes in medication. I think my relapse has also reactivated my Lyme which is making things worse. It seems like Lyme does cause certain CNS/neurological symptoms. For me it's anxiety, depression, insomnia, sensitivity to light/sound/smells, MCS, difficulty concentrating, and impaired memory. I'm not sure if my pain is nerve pain since Gabapentin and Lyrica didn't help. Lyme can damage the collagen tissues so that might be what's going on.

I have no experience with it, but my BIL contracted it, and among other things, one side of his face became paralyzed and sagged. ( this is all he told me). I think the standard antibiotic treatment worked for him, but I believe he was treated early.

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Yeah, that's called Bell's Palsy. It's more common in children infected with Lyme because they're more likely to be bitten on the neck. Treating early stage Lyme is pretty easy compared to late stage/chronic Lyme. Part of the problem is that many people don't experience acute symptoms or even a rash after being bitten so it goes undiagnosed. They're usually just diagnosed with fibromyalgia or CFS. The first time I remember having a rash was over 15 years after I was bitten. Both times the rash appeared a month or two after seeing a chiropractor. One of the places the bacteria hides is in the spinal fluid so I think the adjustments reawakened them. I've heard of other people experiencing an increase/recurrence of symptoms after seeing a chiropractor.

I think I'm having a similar situation. There are cases of unmetabolized folate causing problems, but it's thought to be folic acid. There's some doubt though. Since I've had trouble with methylfolate too, I'm going to suspend my use of it for some months. ( Hopefully, when we get our 23and me results, we'll get a clue.)

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I think my fatigue was probably just from exhaustion and not folic acid. I haven't decided what to do about folates for myself. I've been gradually increasing folinic acid, but not taking any methylfolate. I've been considering taking a high dose of folinic acid all at once just to make sure I'm not one of those people that can't convert folinic acid into methylfolate, but I'm not sure if I'm ready to do any tests just yet. I'm pretty sure folinic acid increased methylation when I tried taking it during my second attempt of methylation. I misread Rich's protocol and thought he meant take 1/4 tablet 4 times a day so I took 800 mcg for almost a week. Most people probably aren't that sensitive although I heard from one person who accidently misread Rich's protocol too. They took 800 mcg all at once and said they stayed up for 36 hours straight. I haven't done anything like that since the days I used to take a lot of Ritalin. I am anxious to find out my 23andme results too. It would be good to know my COMT/VDR Taq status before I start increasing dosages.

I don't know, but he surely had a strong negative reaction, but, if anyone can figure it out, I guess he and dbkita can!

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I actually just asked dbkita about it. He said something about R5P and P5P being "rate-limiting factors". B2 is a cofactor in converting B6 into P5P which is why he mentioned both. I don't know if he's referring just to deficiencies in supplements related to methylation or all nutrients. Freddd said something about all vitamins and minerals potentially being "limiting factors." I'm not sure if they're talking about the same thing (but I asked dbkita so hopefully he'll give me an answer). I do remember someone saying they needed extra potassium after supplementing with boron.

So I found out recently that the way B3 and hydroxocobalamin reduce methylation is by using up SAMe to make the conversion to the active forms. This is from Dr. Ben:

One has to keep in mind that methylation is dynamic and one can shift quickly from under and overmethylated – in a matter of an hr it is possible – or less – especially if utilizing potent nutrients such as methylfolate or methylcobalamin.

We have to keep in mind that there may be other mutations on board – such as COMT. Niacin speeds up COMT which is one reason why it also may be useful. If one speeds up COMT, then things like dopamine and epinephrine get broken down faster. Niacin also is a ‘sponge’ for methyl groups, namely SAMe, because SAMe is required to metabolize niacin.

The B2 helps with the metabolization of folate,( methylation), among other things. (amines too) It has been a very effective anti-inflammatory for me in years past. ( migraines) So, I increased it when I began to have the same type headaches again. I thought the headaches were from the high folate intake alone, but it seems the increase in the methyl groups was also involved. ( I had increased methyl-B12 too.) B2 therapy for migraines may take time to work, several months, I've read. ( I began to feel better after a week or so.)

The B3 does help consume methyl groups, ( learned from Dr.Ben Lynch's site, and other reading), and it has worked well in my case. I've found niacinamide to work just as well as niacin for the symptoms of overmethylation. ( in my case, it also helps the headache)

I finally ordered a 23andme test. Maybe it will help me figure this out. Meanwhile, I'll be very careful with folate.

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I heard from someone else who was taking methylfolate along with high doses of methylcobalamin. They said they started getting headaches so they had to lower their dose of methylcobalmin (from 20 mg down to 5 mg) and also stopped methylfolate altogether.

I heard from someone else who was taking methylfolate along with high doses of methylcobalamin. They said they started getting headaches so they had to lower their dose of methylcobalmin (from 20 mg down to 5 mg) and also stopped methylfolate altogether.

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Hi Lotus;
It looks like I'll be stopping folate supplementation indefinitely. ( tried 100 mcg. the other day-resulted with another very strong headache.)
I'm still needing 5+ mg. methylcobalamin, with some added hydroxocobalamin, because neuropathy returns otherwise.
Regular B2, riboflavin, is still helpful, as well as niacinamide.

I'm not sure how many of us are folate, (supps.), intolerant, but I've noticed a few, ( a minority) I do get ~RDA from foods.

I've been trying to figure this out further, but can only find the same reasons: some people w/ B12 deficiency tend to have a disturbance in folate metabolism. Some people may have genetic polymorphisms that cause this disturbance.

For people with this condition, it may be better to keep the B12 proportion higher, and stay low with folate. ( This is only a guess, from what I've read and experienced.)

Hi Lotus;
It looks like I'll be stopping folate supplementation indefinitely. ( tried 100 mcg. the other day-resulted with another very strong headache.)
I'm still needing 5+ mg. methylcobalamin, with some added hydroxocobalamin, because neuropathy returns otherwise.
Regular B2, riboflavin, is still helpful, as well as niacinamide.

I'm not sure how many of us are folate, (supps.), intolerant, but I've noticed a few, ( a minority) I do get ~RDA from foods.

I've been trying to figure this out further, but can only find the same reasons: some people w/ B12 deficiency tend to have a disturbance in folate metabolism. Some people may have genetic polymorphisms that cause this disturbance.

For people with this condition, it may be better to keep the B12 proportion higher, and stay low with folate. ( This is only a guess, from what I've read and experienced.)

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As I mentioned earlier, I find it interesting that the folate intolerance seems to be happening in reverse for some people taking high doses of methylcobalamin (although these could be isolated incidents). Normally, a person starts out with a folate intolerance, but is gradually able to increase their dose.

Just curious, what type of methylfolate did you take? I found out recently that Metafolin might be twice as potent as generic/racemic methylfolate. Quatrefolic is in the middle.

Also, could the headaches be due to increased histamine? I heard from someone recently who said methylation increased their histamine levels (I don't know their specific symptoms, but maybe I'll ask). I've also heard from two people who experienced headaches at the early stages of methylation.

The headaches people are having could of course be from a variety of causes.

I've read on the pernicious anaemia site, of people getting headaches on the day of their B12 shot. ( I could guess that some may be feeling the effects of increased oxygen transport, for one. I've gotten one type of headache when on oxygen before. It's located in the sinus/forehead area.)

The type of headache I have from inflammation is located most strongly at the base of my skull, radiating to the whole of the head.

Again, if people are taking too many Methyls, then there could be trouble. ( inflammation)

I'm not sure about the histamine reaction, but I think it could be possible with some substance that causes inflammation.

I took solgar's metafolin, methylfolate.
I have also taken new chapters b complex. The folate in it is described as coenzymated and 'active'. ( I agree.)

I think I might also be having symptoms of overmethylation. I have been trying to take b12 (250mcg) every second day, but I think even that might be too much. I've really tried upping my potassium intake, practically the only foods and drinks I ingest are high potassium foods. I am sleeping a lot better lately since increasing potassium and adding magnesium. But I still I feel really anxious, heart palpitations at night, keep checking my pulse, think I'm going to die, hate being alone (which is very out of character for me), not feeling like myself, can't concentrate etc. So then I go off b12 for a few days and gradually I feel myself coming back to normal, like a relief.

What should I do? I can't keep going on like this. It's physically and emotionally exhausting to be anxious all the time.

I think I might also be having symptoms of overmethylation. I have been trying to take b12 (250mcg) every second day, but I think even that might be too much. I've really tried upping my potassium intake, practically the only foods and drinks I ingest are high potassium foods. I am sleeping a lot better lately since increasing potassium and adding magnesium. But I still I feel really anxious, heart palpitations at night, keep checking my pulse, think I'm going to die, hate being alone (which is very out of character for me), not feeling like myself, can't concentrate etc. So then I go off b12 for a few days and gradually I feel myself coming back to normal, like a relief.

What should I do? I can't keep going on like this. It's physically and emotionally exhausting to be anxious all the time.

Can I still heal from taking b12 every few days?

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How much methylfolate are you taking? Although I do tend to get wired even from just B12, it's really the combination of methylfolate and B12 that leads to overmethylation. Additional methyl donors and also B2/R5P and B6/P5P which are involved in folate metabolism can contribute to overmethylation as well.

I'm only taking b12, magnesium and iron supplements at the moment (my ferritin was quite low - 10 - a couple of months ago). I'm not taking any folate at the moment, I think my folate in my blood is quite high.

I'm only taking b12, magnesium and iron supplements at the moment (my ferritin was quite low - 10 - a couple of months ago). I'm not taking any folate at the moment, I think my folate in my blood is quite high.

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I tend to be sensitive too, but I'm not sure why you're experiencing those symptoms. They do sound like symptoms of overmethylation.

I don't think a high folate on your blood test is a good thing. I forget why and I'm too tired to look it up now.

Another option is to take the methylcobalamin orally rather than sublingually since the absorption rate in the gut is much lower. You could start at 250 mcg and gradually increase your dose up to 1000 mcg then try taking 250 mcg sublingually again.

I think I might also be having symptoms of overmethylation. I have been trying to take b12 (250mcg) every second day, but I think even that might be too much. I've really tried upping my potassium intake, practically the only foods and drinks I ingest are high potassium foods. I am sleeping a lot better lately since increasing potassium and adding magnesium. But I still I feel really anxious, heart palpitations at night, keep checking my pulse, think I'm going to die, hate being alone (which is very out of character for me), not feeling like myself, can't concentrate etc. So then I go off b12 for a few days and gradually I feel myself coming back to normal, like a relief.

What should I do? I can't keep going on like this. It's physically and emotionally exhausting to be anxious all the time.

Can I still heal from taking b12 every few days?

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Yes I believe you can heal from taking B12 less often. Most people don't need it as often when they inject.

I agree that it is a good idea to hold off on the folate until it falls back into the normal range. ( This is a different situation than the B12 range.)